Differential inhibition of lipopolysaccharide-induced granulocyte aggregation and prostanoid production by emoxypin.
Emoxypin is known to be an effective membrane-stabilizing 3-oxy-pyridine derivative. We attempted to evaluate its influence on lipopolysaccharide (LPS)-induced granulocyte aggregation and prostanoid production. Granulocytes isolated from rabbit venous blood by dextran sedimentation and Pezcoll gradient centrifugation were stirred in the aggregometer cuvette with emoxypin (5mM), indomethacin (50 microM) or their solvents at 37 degrees C for 2 min. Then S. typhimurium LPS (200 micrograms/ml) was added and the aggregation was traced for 5 min. Thromboxane B2 (TxB2), prostaglandins (PG) E, F2 alpha and 13,14-dihydro-15-keto-PGF2 alpha were determined in supernatants radioimmunochemically. Indomethacin did not affect the pattern of aggregation, whereas emoxypin virtually precluded the response. Granulocytes incubated with LPS produced by the 15th sec and 5th min 1.3 and 2.5 times as much TxB2 respectively as did the intact cells (p less than 0.01). LPS had no effect on PGE production. Fifteen-sec contact of granulocytes with LPS had no significant influence on the formation of PGF2 alpha and its 13,14-dihydro-15-keto metabolite. The amount of PGF2 alpha released into the medium by the end of the 5th min of incubation with LPS was 1.5 times higher than in the control (p less than 0.05); the level of 13,14-dihydro-15-keto-PGF2 alpha was decreased 1.6 times (p less than 0.01). Emoxypin abolished totally LPS-induced TxB2 and PGF2 alpha production. We conclude that aggregation and eicosanoid production are independent manifestations of LPS-induced rabbit granulocyte activation.
Kubatiev
A
A
Department of General Pathology and Pathophysiology, All-Union Institute of Postgraduate Medical Training, Moscow, USSR.
Turgiev
A
A
Smirnov
L
L
Pomoynetsky
V
V
Dumaev
K
K
D000818:Animals; D002449:Cell Aggregation; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010847:Picolines / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D013997:Time Factors
D008070:Lipopolysaccharides; D010847:Picolines; D011453:Prostaglandins; C009820:6-methyl-2-ethyl-3-hydroxypyridine